Abstract
Background
Major depressive disorder (MDD) may be associated with accelerated brain aging (higher
brain age than chronological age). This report evaluated whether brain age is a clinically
useful biomarker by checking its test-retest reliability using magnetic resonance
imaging scans acquired 1 week apart and by evaluating the association of accelerated
brain aging with symptom severity and antidepressant treatment outcomes.
Methods
Brain age was estimated in participants of the EMBARC (Establishing Moderators and
Biosignatures of Antidepressant Response in Clinical Care) study using T1-weighted
structural magnetic resonance imaging (MDD n = 290; female n = 192; healthy control participants n = 39; female n = 24). Intraclass correlation coefficient was used for baseline-to-week-1 test-retest
reliability. Association of baseline Δ brain age (brain age minus chronological age)
with Hamilton Depression Rating Scale–17 and Concise Health Risk Tracking Self-Report
domains (impulsivity, suicide propensity [measures: pessimism, helplessness, perceived
lack of social support, and despair], and suicidal thoughts) were assessed at baseline
(linear regression) and during 8-week-long treatment with either sertraline or placebo
(repeated-measures mixed models).
Results
Mean ± SD baseline chronological age, brain age, and Δ brain age were 37.1 ± 13.3,
40.6 ± 13.1, and 3.1 ± 6.1 years in MDD and 37.1 ± 14.7, 38.4 ± 12.9, and 0.6 ± 5.5
years in healthy control groups, respectively. Test-retest reliability was high (intraclass
correlation coefficient = 0.98–1.00). Higher baseline Δ brain age in the MDD group
was associated with higher baseline impulsivity and suicide propensity and predicted
smaller baseline-to-week-8 reductions in Hamilton Depression Rating Scale–17, impulsivity,
and suicide propensity with sertraline but not with placebo.
Conclusions
Brain age is a reliable and potentially clinically useful biomarker that can prognosticate
antidepressant treatment outcomes.
Keywords
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Article info
Publication history
Published online: September 27, 2022
Accepted:
September 20,
2022
Received in revised form:
September 9,
2022
Received:
April 27,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
